title: Endothelial progenitor cells (EPC) in sepsis with acute renal dysfunction (ARD).
abstract: BACKGROUND
  Sepsis is characterized by systemic microvascular dysfunction. Endothelial progenitor cells (EPCs) are critically involved in maintaining vascular homeostasis under both physiological and pathological conditions. The aim of the present study was to analyze the endothelial progenitor cell system in patients suffering from sepsis with acute renal dysfunction.
  
  
  METHODS
  Patients with newly diagnosed sepsis were recruited from the ICU in a nonrandomized prospective manner. Blood samples were obtained within the first 12 hours after the diagnosis of sepsis. For quantifying endothelial progenitor cells (EPCs), CD133+/Flk-1+ cells were enumerated by cytometric analysis. Analysis of EPC proliferation was performed by a colony-forming units (CFU) assay. Blood concentrations of proangiogenic mediators were measured by ELISA. Acute renal dysfunction was diagnosed according to the Acute Kidney Injury Network (AKIN) criteria. Depending on the overall mean creatinine concentration during the stay at the ICU, patients were either assigned to a 'normal creatinine group' or to a 'high creatinine group'. Survival rates, frequency of dialysis, the simplified acute physiology score (SAPS) II scores, and different laboratory parameters were collected/used for further clinical characterization
  
  
  RESULTS
  Circulating EPCs were significantly higher in all sepsis patients included in the study as opposed to healthy controls. Patients within the 'high creatinine group' showed an even more pronounced EPC increase. In contrast, EPC proliferation was severely affected in sepsis. Neither total circulating EPCs nor EPC proliferation differed between patients requiring dialysis and patients without renal replacement therapy. Cell numbers and cell proliferation also did not differ between surviving patients and patients with sepsis-related death. Serum levels of vascular endothelial growth factor (VEGF), stromal derived factor-1 (SDF-1), and Angiopoietin-2 were higher in sepsis than in healthy controls. Sepsis patients within the 'high creatinine group' showed significantly higher mean serum levels of uric acid.
  
  
  CONCLUSIONS
  Sepsis significantly affects the endothelial progenitor cell system, as reflected by increased EPC numbers, increased concentrations of proangiogenic mediators, and reduced proliferative capacity of the cells. This occurs independently from the frequency of dialysis and from patient survival. Increased serum levels of uric acid are possibly responsible for stronger EPC mobilization in sepsis patients with higher average creatinine levels.
authors.affiliation: Department of Nephrology and Rheumatology, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075 Göttingen, Germany. spatschan@gmail.com
authors.forename: Susann A
authors.initials: SA
authors.lastname: Patschan
authors.forename: Daniel
authors.initials: D
authors.lastname: Patschan
authors.forename: Johanna
authors.initials: J
authors.lastname: Temme
authors.forename: Peter
authors.initials: P
authors.lastname: Korsten
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Wessels
authors.forename: Michael
authors.initials: M
authors.lastname: Koziolek
authors.forename: Elvira
authors.initials: E
authors.lastname: Henze
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Müller
mesh_terms: D000208:Acute Disease; D000368:Aged; D016022:Case-Control Studies; D002452:Cell Count; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007674:Kidney Diseases / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D013234:Stem Cells / Q000166:cytology*